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Monocytes, but not T cells, respond to insulin with Akt(S473) phosphorylation independent of the donor glucometabolic state
Author(s) -
Thewissen M. M.,
Gaar J.,
Boer A. Th.,
Munsters M. J.,
Blaak E. E.,
Duijvestijn A.
Publication year - 2014
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2498
Subject(s) - insulin resistance , medicine , insulin , endocrinology , monocyte , type 2 diabetes , insulin receptor , immune system , protein kinase b , peripheral blood mononuclear cell , diabetes mellitus , chemistry , biology , phosphorylation , immunology , biochemistry , in vitro
Background Obesity is associated with insulin resistance and chronic low‐grade inflammation. Insulin has been described to have anti‐inflammatory effects in immune cells. Therefore, insulin resistance in immune cells can be expected to have important consequences for immune function. Here, we investigate whether freshly isolated monocytes and T cells, isolated from study subjects with a normal or disturbed glucometabolic state, respond to insulin with phosphorylation of Akt, a key molecule in the insulin signalling pathway. Methods A total of 25 study subjects were enrolled in the study. An oral glucose tolerance test (OGTT) was performed, and from fasting insulin and glucose, the homeostasis model assessment of insulin resistance (HOMA‐IR) index was calculated. Peripheral blood mononuclear cells were isolated from heparinized blood and phenotypically characterized by flow cytometry. Basal and insulin‐induced fractions of pAkt(S473)‐positive monocytes and T cells were determined by Phosflow. Results On the basis of the OGTT, 11 subjects were classified as normal glucose tolerant (NGT), 9 had an impaired glucose metabolism (IGM) and 5 had type 2 diabetes (T2DM). The fraction of pAkt(S473)positive‐T cells and monocytes, in the absence of insulin, was low in all subjects. Incubation with insulin did not induce Akt phosphorylation in CD4 + and CD8 + T cells in normal subjects. However, in the monocyte fraction, an insulin‐dose‐dependent increase of the pAkt(S473)positive‐cell fraction was observed. This response did not differ between NGT, IGM and T2DM and was not correlated with HOMA‐IR. Conclusions In this study, we show that freshly isolated monocytes, but not T cells, are insulin‐sensitive cells and that this insulin sensitivity of monocytes is not negatively affected by the glucometabolic state of the donor. Copyright © 2013 John Wiley & Sons, Ltd.